Transcriptional Bursting Kinetics of Incomplete Dosage Compensation in ZW Sex Determining System
(2021) BINP51 20202Degree Projects in Bioinformatics
- Popular Abstract
- Transcriptional Burst Kinetics of Dosage Compensation in Chicken
Sex chromosome combinations are different between sexes in many animal species. In therian mammals, females hold XX and males hold XY, which is called male heterogametic system. In birds, the sex chromosome system is female heterogametic (ZZ in males and ZW in females). The gene dosage imbalance between sexes (Xm:XXf or Zf:ZZm) and between sex chromosome and autosomes (Xm:AAm or Zf:AAf) is believed to disrupt gene regulatory networks and could be restored by dosage compensation (DC). DC mechanisms are hugely diverse across species, termed as “complete” and “incomplete” depending on whether dosage imbalance is fully restored or not.
There have been a large number of... (More) - Transcriptional Burst Kinetics of Dosage Compensation in Chicken
Sex chromosome combinations are different between sexes in many animal species. In therian mammals, females hold XX and males hold XY, which is called male heterogametic system. In birds, the sex chromosome system is female heterogametic (ZZ in males and ZW in females). The gene dosage imbalance between sexes (Xm:XXf or Zf:ZZm) and between sex chromosome and autosomes (Xm:AAm or Zf:AAf) is believed to disrupt gene regulatory networks and could be restored by dosage compensation (DC). DC mechanisms are hugely diverse across species, termed as “complete” and “incomplete” depending on whether dosage imbalance is fully restored or not.
There have been a large number of studies on DC in therian mammals, which employed microarray and RNA sequencing (RNA-seq) techniques to quantify and compare gene expression level on sex chromosomes and autosomes. In these studies, complete DC pattern was found in chicken, showing that one of two X chromosomes in females is randomly inactivated and X-linked gene expression on the single activated X chromosome in both sexes is increased to autosomal biallelic gene level. In particular, Larsson et al. (2019) inferred transcriptional burst kinetics of DC in mice to conclude that X chromosome upregulation is driven by burst frequency. In birds, previous microarray and RNA-seq studies have proved the incomplete DC pattern, meaning that Z chromosome genes are still expressed 20-50% higher in males than that in females. Additionally, corresponding burst kinetics study of incomplete DC in chicken is still lack.
In my thesis project, I analysed bulk RNA-seq from several tissues and single cell RNA-seq (scRNA-seq) data from fibroblast cells in chicken to investigate the incomplete DC pattern and corresponding allelic transcriptional burst kinetics. Gene expression profiles showed identical patterns of DC in different tissues. With a confident strain-specific SNP dataset, allelic expression level of scRNA-seq data were quantified and subsequently used to infer burst kinetics parameters, burst size and burst frequency, which describe the characteristics of transcriptional burst. Linear regression tests showed that burst frequency had more effect on allelic expression than burst size, and Wilcoxon test showed no difference between autosomes and Z chromosome and between sexes except higher burst frequency of dosage-sensitive Z chromosome genes in females. Finally, core promoter elements effect analysis exhibited synergistic improving effect of TATA box and Initiator element on burst size.
In conclusion, my results demonstrated that incomplete DC widely present in different tissues in chicken. Burst kinetics results weakly and preliminarily explained how DC between sexes achieved by altered burst frequency of dosage-sensitive genes. In addition, promoter elements effect analysis provided the approach to investigate the transcriptional regulatory mechanisms with burst kinetics features.
Master’s Degree Project in Bioinformatics 45 credits 2021
Department of Biology, Lund University
Advisor: Björn Reinius
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/9067435
@misc{9067435,
author = {{Xin, Xian}},
language = {{eng}},
note = {{Student Paper}},
title = {{Transcriptional Bursting Kinetics of Incomplete Dosage Compensation in ZW Sex Determining System}},
year = {{2021}},
}